Experiments show a much-feared bird flu can mutate and spread among mammals

Margaret Munro, Postmedia News06.21.2012

Ron Fouchier, a virologist at the Erasmus Medical Centre in the Netherlands, has created an international furor by genetically modifying the dreaded H5N1 avian flu virus so it could spread between ferrets by airborne transmission. The lab experiments suggest the virus needs only a few more mutations to have the potential to cause a pandemic.

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His genetic modifications of the dreaded avian flu so alarmed U.S. officials they deemed his experiment too dangerous to publish, triggering an intense international debate about "doomsday" viruses escaping from the lab or falling into bioterrorists' hands.

After being held up for months, details of the Dutch experiment were released Thursday by the journal Science. Bruce Alberts, the journal's editor-in-chief, says he hopes publishing the contentious research "will help to make the world safer."

It has already prompted an international review of "dual-use" technologies that can be used for good or evil.

But perhaps more important, says scientists, the Dutch experiments show the much-feared H5N1 bird flu is able to mutate and spread among mammals — and presumably humans.

They warn it may take just three more mutations to viruses already in circulation to trigger a pandemic.

H5N1 is not yet contagious between people but it is a big concern to public health officials because it's so deadly. Almost half the people infected with the virus have died, a much higher mortality rate than the Spanish flu that killed millions of people in the pandemic of 1918 and 1919.

Fouchier's experiments were done in a secure laboratory at Erasmus Medical Centre in the Netherlands, and were funded and approved by the U.S. National Institutes of Health.

The research involved exposing ferrets, which are considered the best proxy for humans when studying the flu, to H5N1 that had been genetically modified with mutations the scientists expected would increase the virus' affinity for mammalian cells.

They put the modified virus directly into the ferrets' noses then repeatedly transferred the virus to more ferrets to see how it evolved. Then they placed cages containing healthy and infected ferrets beside each other and most of the healthy ferrets became infected with influenza virus.

"We show that as little as five mutations, but certainly less than 10, are sufficient to make H5N1 virus airborne," Fouchier told reporters in a teleconference.

In a second paper in Science, also released Thursday, Fouchier and his colleagues report two of the mutations used in the ferret experiment are already circulating in avian flu virus common in birds. The scientists say the virus may only require three more mutations to become transmissible by respiratory droplets between mammals and humans.

All of which make "a virus evolving in nature a potentially serious threat," they report.

The scientists say they don't know how long it would take for such a transmissible virus to emerge, but Derek Smith at the University of Cambridge says "it is absolutely within the realm of possibility that they could evolve."

Earl Brown, executive director of the Emerging Pathogens Research Centre at the University of Ottawa, says one of the intriguing, and reassuring aspects of the Dutch experiments is that virus seemed to lose virulence as it become more transmissible.

The virus made the ferrets sick but it did not kill the animals when the virus was transmitted by airborne transmission from cage to cage, the scientists report.

"The best guess would be that our virus would also be airborne in humans, but would not be lethal when humans are exposed to virus via aerosols," Fouchier says via email.

Brown, who studies flu virulence in mice, feels the biosecurity concerns over the experiments were overblown and says the viruses that evolved in the ferret experiments wouldn't pose much of bioterrorist threat.

The furor over the Dutch experiment, and related research in the U.S., began last fall when Fouchier presented some of his findings at a flu conference. He later described his team's creation as "probably one of the most dangerous viruses you can make."

The U.S. National Science Advisory Board for Biosecurity stepped in and recommended in December the reports about the new viruses not be published unless certain details were withheld.

The World Health Organization disagreed and said in February the flu experiments should be published in full saying the information could help improve anti-flu drugs and vaccines and surveillance for dangerous changes in avian flu viruses in the wild.

The U.S biosecurity panel reversed itself in March clearing the way for the publication of experiments.

The U.S. government and WHO are now studying how best to control "dual use research of concern."

In response to the controversy the Public Health Agency of Canada announced in February that it would confine any mutate strains of H5N1 used in Canada to maximum-security laboratories.

Frank Plummer, PHAC's chief science adviser, says no one is currently working on H5N1 in Canada. But he says strains of the virus are stored in the National Microbiology Laboratory in Winnipeg and Canadian researchers want keep open the option of working on the virus.

He says some of Canada's "high containment people" may participate in the international talks on how best proceed with dual-use research.

"There is a lot of discussion about so-called synthetic biology and what to do about it," Plummer said in an interview. "Obviously you don't want these technologies in the wrong hands, but also you don't want to impede legitimate research. So it's sort of a delicate balance."

Brown, at the University of Ottawa, says the " big question now" is whether avian flu will mutate to transmit in humans. "The natural experiment is underway out there but it hasn't ticked over yet," he says.

"It really comes down to where the mutations are, and how they enable a virus to change its properties," says Brown.

mmunro@postmedia.com

Twitter.com/margaretmunro

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Experiments show a much-feared bird flu can mutate and spread among mammals

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